Although numerous heterocyclic compounds have been tested in recent years for anticonvulsant activity, to date there is no reference to any studies on the 1,2,3-triazoline heterocycles. Also, very little is known about the anticonvulsant potential of the closely related 1H-1,2,3-triazoles and aziridines. We have discovered that by addition of CH2N2 to Schiff bases in the presence of water as a catalyst, both aryl and heteroaryl substituted triazolines could be prepared conveniently in large yields. Preliminary screening studies of 1,5-substituted triazolines and triazoles (by our versatile KMnO4 oxidation of triazolines using phase-transfer catalysis), using the scMet and MES tests of the Anticonvulsant Screening Project of NINCDS, have led to the identification of potent anticonvulsant activity (ED less than 30-100 mg/kg;P.I. greater than 3-10) in seven compounds, six of which are 1-aryl-5-heteroaryl-substituted. While the triazolines are effective in the Met test, the triazoles are potent in the MES and/or Met tests. One triazoline, subjected to advanced screens, has ED50(mg/kg) of 43.53 in scMet and 12.06 in scBic. and respective P.I. of 26 and 93.9; is active upon oral administration in the mouse, and compares well with marketed antiepileptic drugs. Our objective is to use these compounds as active "leads" for the rational design of potentially more potent analogs utilizing the Topliss manual method for substituent selection on the 1-Ph ring using compound groups. Also, different heterocyclic groups (pyridyl, piperidyl or piperazinyl) will be incorporated in the 5-position of the triazoline ring, and for each 5-substituent the optimum subtitution on the 1-Ph ring will be determined using the Topliss analog scheme. The corresponding triazoles and aziridines (from triazoline photolysis) will also prepared and screened. Structure-activity relations in the different classes will be evaluated, and the results correlated with experimentally determined octanol-water partition coefficients. It is hoped that the present studies will help to develop better drugs for epilepsy in humans.